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Autoimmun Rev. 2014 Mar;13(3):272-80. doi: 10.1016/j.autrev.2013.10.010. Epub 2013 Nov 2.

Chemokine (C-X-C motif) ligand (CXCL)10 in autoimmune diseases.

Author information

1
Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, 56126 Pisa, Italy. Electronic address: alessandro.antonelli@med.unipi.it.
2
Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, 56126 Pisa, Italy. Electronic address: sm.ferrari@int.med.unipi.it.
3
Department of Medical, Surgical, Maternal, Pediatric and Adult Sciences, University of Modena and Reggio Emilia, Via del Pozzo, 71, 41100 Modena, Italy. Electronic address: giuggioli.dilia@policlinico.mo.it.
4
Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, 56126 Pisa, Italy. Electronic address: ferranni@ifc.cnr.it.
5
Department of Medical, Surgical, Maternal, Pediatric and Adult Sciences, University of Modena and Reggio Emilia, Via del Pozzo, 71, 41100 Modena, Italy. Electronic address: clferri@unimore.it.
6
Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, 56126 Pisa, Italy. Electronic address: poupak@int.med.unipi.it.

Abstract

(C-X-C motif) ligand (CXCL)10 (CXCL10) belongs to the ELR(-) CXC subfamily chemokine. CXCL10 exerts its function through binding to chemokine (C-X-C motif) receptor 3 (CXCR3), a seven trans-membrane receptor coupled to G proteins. CXCL10 and its receptor, CXCR3, appear to contribute to the pathogenesis of many autoimmune diseases, organ specific (such as type 1 diabetes, autoimmune thyroiditis, Graves' disease and ophthalmopathy), or systemic (such as rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, mixed cryoglobulinemia, Sjögren syndrome, or systemic sclerosis). The secretion of CXCL10 by cluster of differentiation (CD)4+, CD8+, natural killer (NK) and NK-T cells is dependent on interferon (IFN)-γ, which is itself mediated by the interleukin-12 cytokine family. Under the influence of IFN-γ, CXCL10 is secreted by several cell types including endothelial cells, fibroblasts, keratinocytes, thyrocytes, preadipocytes, etc. Determination of high level of CXCL10 in peripheral fluids is therefore a marker of host immune response, especially T helper (Th)1 orientated T-cells. In tissues, recruited Th1 lymphocytes may be responsible for enhanced IFN-γ and tumor necrosis factor-α production, which in turn stimulates CXCL10 secretion from a variety of cells, therefore creating an amplification feedback loop, and perpetuating the autoimmune process. Further studies are needed to investigate interactions between chemokines and cytokines in the pathogenesis of autoimmune diseases and to evaluate whether CXCL10 is a novel therapeutic target in various autoimmune diseases.

KEYWORDS:

AT; Autoimmune thyroiditis; CCL; CD; CIA; CS; CSF; CXCL; CXCL10; CXCR3; Circulating CXCL10 levels; Cryoglobulinemia; GAD; GD; GO; Graves; Graves' disease; Graves' ophthalmopathy; Graves’ disease; Graves’ ophthalmopathy; Gtx; Hepatitis C virus infection associated mixed cryoglobulinemia; IFN; IFN-γ-induced protein 10; IL; IP-10; JIA; Juvenile idiopathic arthritis; MC; MC+HCV; MCP-1; MDC/CCL22; MIG; MMI; MP; NF-kB; NK; NPSLE; PPAR-γ; PTC; Papillary thyroid cancer; Peroxisome proliferator-activated receptor-γ; PsA; Psoriatic arthritis; RA; RANKL; RANTES; RET/PTC; Rheumatoid arthritis; SF; SLE; SS; SSc; ST; Sjögren syndrome; Systemic lupus erythematosus; Systemic sclerosis; T helper; T1D; TARC/CCL17; TFC; TNF; TNG; TR; Th; Thyroid follicular cells; Thyroiditis; Toxic nodular goiter; Type 1 diabetes; autoimmune thyroiditis; cerebrospinal fluid; chemokine (C–C motif) ligand; chemokine (C–X–C motif) ligand; chemokine (C–X–C motif) receptor 3; circulating CXCL10 levels; cluster of differentiation; collagen-induced arthritis; corticosteroid; glutamic acid decarboxylase; hepatitis C virus infection associated mixed cryoglobulinemia; hyperthyroid GD; interferon; interleukin; juvenile idiopathic arthritis; macrophage-derived chemokine/CCL22; methimazole; methylprednisolone; mixed cryoglobulinemia; monocyte chemotactic protein-1; monokine induced by IFN-γ; natural killer; neuropsychiatric SLE; normal T cell expressed and secreted; nuclear factor-kappa B; papillary thyroid cancer; peroxisome proliferator-activated receptor-γ; psoriatic arthritis; rearranged in transformation/PTC; receptor activator of nuclear factor kappa-B ligand; rheumatoid arthritis; sCXCL10; synovial fluid; synovial tissue; systemic lupus erythematosus; systemic sclerosis; teleradiotherapy; thymus and activation regulated chemokine/CCL17; thyroid follicular cells; toxic nodular goiter; tumor necrosis factor; type 1 diabetes

PMID:
24189283
DOI:
10.1016/j.autrev.2013.10.010
[Indexed for MEDLINE]

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